Mass spectrometers have become one of the most widely utilized instruments for analyzing chemical entities dissolved in liquids. As a consequence of the valuable information derived from such analyses, there is an incentive to process increased numbers of samples in shorter periods of time in industrial, academic, and government-based laboratories. High speed serial systems as well as systems capable of introducing multiple samples simultaneously introduced into a mass spectrometer in a parallel fashion have been reported.
The high-speed fast serial approach does not attempt to parallel sample introduction streams. Instead, it assures that samples enter the mass spectrometer in a sequential fashion. The mass spectrometric measurement on each sample remains uninterrupted as the sample enters and passes through the mass spectrometer. The fast serial technique conducts both sample introduction and measurement in a sequential manner as rapidly as fluid transfer constraints will allow. However, they are always constrained by the relatively slow time scale of sequential rather than parallel sample introduction. Some examples of this approach have been published in the literature (Hiller, et al. Rapid Comm. Mass Spectrom. 14, 2034-2038, 2000). Occasionally multiple sprayer systems are incorporated into fast serial introduction systems (see above reference) to ameliorate some of the fluidic delays encountered in single channel sprayers but they are still operated in a serial sample introduction mode with similar time constraints.
There are three general categories of methods for the introduction of multiple samples simultaneously into a mass spectrometer in a parallel fashion. All of the methods share one feature in common, resulting from the fact that the process of obtaining a mass spectrometric measurement on a sample is very fast, typically milliseconds, compared to the rate at which samples can be introduced into the ionization region of the mass spectrometer, typically seconds. Thus, in situations where a plurality of samples are simultaneously entering a mass spectrometer over a relatively long period of time, a series of fast sequential mass spectrometric measurements can be made on each of the multiple samples entering the spectrometer. Although multiple samples enter the mass spectrometer, all of the samples must enter through separate and distinct fluid channels so that each channel may be rapidly turned on and off, by some means, in synchrony with the mass spectrometric measurement. In this way, every mass spectrometric measurement may be associated with a particular sample from a particular channel in an unequivocal fashion.
The three general categories of methods for introducing multiple parallel samples are similar in that the mass spectrometric measurements are taken in rapid sequence, i.e. sequentially. However, from a sample introduction point of view, they are all parallel in nature. Since mass spectrometric measurements are very fast relative to sample introduction speeds (milliseconds versus seconds), the sample introduction becomes the bottleneck for fast analyses, so the sequential mass spectrometric measurements do not negate the speed advantage afforded by parallel sample introduction systems. With parallel systems, the mass spectrometric measurement on each sample is constantly interrupted as the system rapidly cycles from channel to channel. This requires good synchronization between the channel selection and the mass spectrometric measurement so that the data can be easily interpreted without ambiguity regarding the association of a particular measurement and the sample travelling in the selected channel.
The three categories of methods to multiplex sample introduction differ in the means by which they gate i.e. turn on and off, the separate sample channels and thus obtain synchrony with the mass spectrometer. The first method segregates each separate channel into a distinct ion beam within the vacuum system of the mass spectrometer, and deflects or focuses the ion beam at the appropriate time. The second method uses a physical shutter driven by a rotating device such as a stepper motor or other mechanical device to physically block the ionization spray occurring at atmospheric pressure. A derivative of this method physically moves individual sprayers into focus also using a rotating device. The third method is generally referred to as fluidic selector. Each of these approaches are illustrated and discussed in further detail below.
Although the above-described methods permit the introduction of parallel fluidic streams into the mass spectrometer, problems exist in that the gating elements used to select sample channels cause dispersion in the fluid sample streams. As will be appreciated, improvements in the manner by which fluid sample streams are delivered to a mass spectrometer are desired.
It is therefore an object of the present invention to provide a novel sample introduction device and method for introducing one or more fluid sample streams into a mass spectrometer.